Second Björn Folkow Award Lecture. The renin-angiotensin system: new surprises ahead

There is considerable evidence that the vascular renin-angiotensin systems contribute to the structural adaptations of hypertension. This article describes recent clinical data on local angiotensin formation in different vascular beds together with clinical findings that support the possible involvement of prorenin, in addition to renin, in local angiotensin formation. Our measurements of steady-state arterial and venous plasma levels of systemically infused 125I-angiotensin (Ang) I and of endogenous Ang I across a number of vascular beds in untreated and captopril-treated hypertensive subjects have revealed that most of the Ang I production in the forearm, leg, and kidney appears to take place at tissue sites and not in circulating plasma. This local production depends mainly on plasma-derived renin of renal origin, however. When we also measured the levels of systemically infused 251I-Ang II across these vascular beds, we found that although a substantial fraction of Ang II in the regional veins was derived from new production and not from arterial delivery, most could be attributed to the conversion of arterially delivered Ang I. The exception was in the kidney, where about 70% of venous Ang II appeared to have been derived from Ang I produced in renal tissue. Thus, our results indicate that extrarenally synthesized renin does not contribute significantly to circulating levels of Ang I and II. The proposal that prorenin contributes to local extrarenal angiotensin formation is based on evidence that prorenin production occurs in a variety of tissues other than the kidney. This extrarenal production may lead to high levels of circulating prorenin, as seen in many diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)